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      Tobacco and oral squamous cell carcinoma: A review of carcinogenic pathways

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          Abstract

          INTRODUCTION

          Tobacco is one of the most important risk factors for premature death globally. More than 60 toxic chemicals in tobacco can invade the body’s various systems. Oral squamous cell carcinoma (OSCC) is a pathological type of oral cancer, accounting for over 90% of oral cancers. A vast quantity of scientific, clinical and epidemiological data shows that tobacco is associated with the development of oral squamous cell carcinoma, and its carcinogenic pathways may be complicated.

          METHODS

          We conducted a thorough electronic search by Cochrane, EMBASE and PubMed to identify relevant studies. Studies published up to the end of October 2018 were included. After assessing and selecting articles based on eligibility criteria, studies were classified and elaborated according to the pathogenesis.

          RESULTS

          Tobacco as an important risk factor can cause epigenetic alteration of oral epithelial cells, inhibit multiple systemic immune functions of the host, and its toxic metabolites can cause oxidative stress on tissues and induce OSCC. In addition, some specific viruses such as EBV and HPV are thought to play a role in the development of OSCC.

          CONCLUSIONS

          Oral cancer ranks eighth among the most common causes of cancer-related deaths worldwide, and tobacco is one the most important carcinogenic factors of OSCC. This review of the literature attempts to provide directions and ideas for future related research, and emphasizes the need for efforts to reduce tobacco consumption.

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          Most cited references63

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          Estimates of global mortality attributable to smoking in 2000.

          Smoking is a risk factor for several diseases and has been increasing in many developing countries. Our aim was to estimate global and regional mortality in 2000 caused by smoking, including an analysis of uncertainty. Following the methods of Peto and colleagues, we used lung-cancer mortality as an indirect marker for accumulated smoking risk. Never-smoker lung-cancer mortality was estimated based on the household use of coal with poor ventilation. Relative risks were taken from the American Cancer Society Cancer Prevention Study, phase II, and the retrospective proportional mortality analysis of Liu and colleagues in China. Relative risks were corrected for confounding and extrapolation to other regions. We estimated that in 2000, 4.83 (uncertainty range 3.94-5.93) million premature deaths in the world were attributable to smoking; 2.41 (1.80-3.15) million in developing countries and 2.43 (2.13-2.78) million in industrialised countries. 3.84 million of these deaths were in men. The leading causes of death from smoking were cardiovascular diseases (1.69 million deaths), chronic obstructive pulmonary disease (0.97 million deaths), and lung cancer (0.85 million deaths). Smoking was an important cause of global mortality in 2000. In view of the expected demographic and epidemiological transitions and current smoking patterns in the developing world, the health loss due to smoking will grow even larger unless effective interventions and policies that reduce smoking among men and prevent increases among women in developing countries are implemented.
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            The p53-p21-DREAM-CDE/CHR pathway regulates G2/M cell cycle genes

            The tumor suppressor p53 functions predominantly as a transcription factor by activating and downregulating gene expression, leading to cell cycle arrest or apoptosis. p53 was shown to indirectly repress transcription of the CCNB2, KIF23 and PLK4 cell cycle genes through the recently discovered p53-p21-DREAM-CDE/CHR pathway. However, it remained unclear whether this pathway is commonly used. Here, we identify genes regulated by p53 through this pathway in a genome-wide computational approach. The bioinformatic analysis is based on genome-wide DREAM complex binding data, p53-depedent mRNA expression data and a genome-wide definition of phylogenetically conserved CHR promoter elements. We find 210 target genes that are expected to be regulated by the p53-p21-DREAM-CDE/CHR pathway. The target gene list was verified by detailed analysis of p53-dependent repression of the cell cycle genes B-MYB (MYBL2), BUB1, CCNA2, CCNB1, CHEK2, MELK, POLD1, RAD18 and RAD54L. Most of the 210 target genes are essential regulators of G2 phase and mitosis. Thus, downregulation of these genes through the p53-p21-DREAM-CDE/CHR pathway appears to be a principal mechanism for G2/M cell cycle arrest by p53.
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              Melanoma cell expression of Fas(Apo-1/CD95) ligand: implications for tumor immune escape.

              Malignant melanoma accounts for most of the increasing mortality from skin cancer. Melanoma cells were found to express Fas (also called Apo-1 or CD95) ligand (FasL). In metastatic lesions, Fas-expressing T cell infiltrates were proximal to FasL+ tumor cells. In vitro, apoptosis of Fas-sensitive target cells occurred upon incubation with melanoma tumor cells; and in vivo, injection of FasL+ mouse melanoma cells in mice led to rapid tumor formation. In contrast, tumorigenesis was delayed in Fas-deficient lpr mutant mice in which immune effector cells cannot be killed by FasL. Thus, FasL may contribute to the immune privilege of tumors.
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                Author and article information

                Journal
                Tob Induc Dis
                Tob Induc Dis
                TID
                Tobacco Induced Diseases
                European Publishing on behalf of the International Society for the Prevention of Tobacco Induced Diseases (ISPTID)
                2070-7266
                1617-9625
                12 April 2019
                2019
                : 17
                : 29
                Affiliations
                [1 ]Department of Pediatric Dentistry, State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
                Author notes
                CORRESPONDENCE TO Ruijie Huang. Department of Pediatric Dentistry, State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China. E-mail: ruijmhuang@ 123456gmail.com ORCID ID: https://orcid.org/0000-0003-3211-518X
                [*]

                Contributed equally

                Article
                29
                10.18332/tid/105844
                6752112
                31582940
                4e03bb71-b078-4e43-a173-f4cf0b5ca4d3
                © 2019 Jiang X

                This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 International License.

                History
                : 28 December 2018
                : 18 February 2019
                : 20 March 2019
                Categories
                Review Paper

                Respiratory medicine
                tobacco,smoking,oral squamous cell carcinoma,carcinogenic pathways
                Respiratory medicine
                tobacco, smoking, oral squamous cell carcinoma, carcinogenic pathways

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